Edgewise Therapeutics Announces Positive Top-Line Results from Phase 2 CIRRUS-HCM Four-Week Trial of EDG-7500 in Hypertrophic Cardiomyopathy (HCM)
Edgewise Therapeutics (EWTX) announced positive top-line results from its Phase 2 CIRRUS-HCM four-week trial of EDG-7500 in patients with Hypertrophic Cardiomyopathy (HCM). The trial demonstrated significant efficacy in both obstructive and nonobstructive HCM patients.
Key findings for obstructive HCM patients at 100mg dose include:
- 71% reduction in resting LVOT gradients
- 58% reduction in provokable gradients
- 62% reduction in NT-proBNP heart failure biomarker
- 78% of participants improved by ≥1 NYHA Class
For nonobstructive HCM patients, the 100mg dose achieved a 42% reduction in NT-proBNP. The drug was generally well-tolerated, with most adverse events being mild to moderate. The company plans to initiate Phase 3 trials in the first half of 2026.
Edgewise Therapeutics (EWTX) ha annunciato risultati positivi preliminari dal suo trial di Fase 2 CIRRUS-HCM della durata di quattro settimane sull'EDG-7500 in pazienti con Cardiomiopatia Ipertrofica (HCM). Il trial ha dimostrato un'efficacia significativa sia nei pazienti con HCM ostruttiva che in quelli con HCM non ostruttiva.
I risultati chiave per i pazienti con HCM ostruttiva alla dose di 100mg includono:
- riduzione del 71% dei gradienti LVOT a riposo
- riduzione del 58% dei gradienti provocabili
- riduzione del 62% del biomarker di insufficienza cardiaca NT-proBNP
- il 78% dei partecipanti ha mostrato un miglioramento di ≥1 Classe NYHA
Per i pazienti con HCM non ostruttiva, la dose di 100mg ha raggiunto una riduzione del 42% del NT-proBNP. Il farmaco è stato generalmente ben tollerato, con la maggior parte degli eventi avversi classificati come lievi o moderati. L'azienda prevede di avviare studi di Fase 3 nella prima metà del 2026.
Edgewise Therapeutics (EWTX) anunció resultados positivos preliminares de su ensayo de Fase 2 CIRRUS-HCM de cuatro semanas sobre el EDG-7500 en pacientes con Miocardiopatía Hipertrófica (HCM). El ensayo demostró una eficacia significativa tanto en pacientes con HCM obstructiva como en aquellos con HCM no obstructiva.
Los hallazgos clave para los pacientes con HCM obstructiva a la dosis de 100mg incluyen:
- reducción del 71% en los gradientes LVOT en reposo
- reducción del 58% en gradientes provocables
- reducción del 62% en el biomarcador de insuficiencia cardíaca NT-proBNP
- el 78% de los participantes mejoró en ≥1 Clase NYHA
Para los pacientes con HCM no obstructiva, la dosis de 100mg logró una reducción del 42% en NT-proBNP. El medicamento fue generalmente bien tolerado, siendo la mayoría de los eventos adversos leves a moderados. La empresa planea iniciar ensayos de Fase 3 en la primera mitad de 2026.
엣지와이즈 테라퓨틱스 (EWTX)는 비대 심근병증 (HCM) 환자를 대상으로 한 EDG-7500의 4주간의 2상 CIRRUS-HCM 시험에서 긍정적인 주요 결과를 발표했습니다. 이 시험은 HCM의 폐쇄형 및 비폐쇄형 환자 모두에서 상당한 효능을 입증했습니다.
폐쇄형 HCM 환자에 대한 주요 발견은 100mg 용량에서 다음과 같습니다:
- 안정 시 LVOT 기울기 71% 감소
- 유발 가능한 기울기 58% 감소
- 심부전 바이오마커 NT-proBNP 62% 감소
- 참여자의 78%가 NYHA 클래스 ≥1 개선
비폐쇄형 HCM 환자의 경우, 100mg 용량에서 NT-proBNP가 42% 감소했습니다. 이 약물은 일반적으로 잘 견뎌졌으며, 대부분의 부작용은 경미하거나 중간 정도의 수준이었습니다. 회사는 2026년 상반기에 3상 시험을 시작할 계획입니다.
Edgewise Therapeutics (EWTX) a annoncé des résultats préliminaires positifs de son essai de phase 2 CIRRUS-HCM de quatre semaines sur l'EDG-7500 chez des patients atteints de cardiomyopathie hypertrophique (HCM). L'essai a démontré une efficacité significative tant chez les patients HCM obstructifs que non obstructifs.
Les principales conclusions pour les patients HCM obstructifs à une dose de 100 mg incluent:
- réduction de 71% des gradients LVOT au repos
- réduction de 58% des gradients provoqués
- réduction de 62% du biomarqueur de l'insuffisance cardiaque NT-proBNP
- 78% des participants ont montré une amélioration de ≥1 classe NYHA
Pour les patients HCM non obstructifs, la dose de 100 mg a permis une réduction de 42% du NT-proBNP. Le médicament a généralement été bien toléré, la plupart des événements indésirables étant légers à modérés. L'entreprise prévoit de commencer les essais de phase 3 au cours de la première moitié de 2026.
Edgewise Therapeutics (EWTX) hat positive vorläufige Ergebnisse aus seiner vierwöchigen Phase-2-Studie CIRRUS-HCM zu EDG-7500 bei Patienten mit hypertropher Kardiomyopathie (HCM) bekannt gegeben. Die Studie zeigte eine signifikante Wirksamkeit sowohl bei obstruktiven als auch bei nicht obstruktiven HCM-Patienten.
Wichtige Ergebnisse für obstruktive HCM-Patienten bei einer Dosis von 100 mg umfassen:
- 71% Reduktion der LVOT-Gradienten im Ruhezustand
- 58% Reduktion der provokanten Gradient
- 62% Reduktion des NT-proBNP-Biomarkers für Herzinsuffizienz
- 78% der Teilnehmer verbesserten sich um ≥1 NYHA-Klasse
Für nicht obstruktive HCM-Patienten erreichte die Dosis von 100 mg eine Reduktion von 42% im NT-proBNP. Das Medikament wurde im Allgemeinen gut vertragen, wobei die meisten unerwünschten Ereignisse mild bis moderat waren. Das Unternehmen plant, in der ersten Hälfte des Jahres 2026 mit den Phase-3-Studien zu beginnen.
- Strong efficacy data with 71% reduction in resting LVOT gradients
- 78% of participants improved by ≥1 NYHA Class in cardiac function
- Significant 62% reduction in heart failure biomarker NT-proBNP
- Drug demonstrated good safety profile without systolic dysfunction
- Clear path to Phase 3 trials with timeline established
- Two patients experienced serious adverse events requiring cardioversion
- One participant discontinued treatment due to dizziness
- Phase 3 trials won't begin until first half of 2026
Insights
Edgewise's EDG-7500 Phase 2 results represent a significant therapeutic breakthrough for Hypertrophic Cardiomyopathy treatment. The 71% reduction in resting LVOT gradients and 58% reduction in provokable gradients at the 100mg dose are remarkably robust for a mid-stage trial. Most impressive is achieving these results without compromising left ventricular ejection fraction—a critical safety advantage over existing approaches.
The 62% reduction in NT-proBNP (heart failure biomarker) and substantial 23-point increase in quality of life scores (KCCQ-OSS) demonstrate meaningful clinical impact beyond just physiological measurements. Perhaps most telling is that 67% of patients became asymptomatic (NYHA Class I) after only four weeks of treatment.
Efficacy in both obstructive and nonobstructive HCM variants expands the potential patient population substantially. While the atrial fibrillation events require monitoring, they appeared at rates comparable to other cardiac myosin inhibitors in development.
The dual mechanism addressing both obstruction and diastolic dysfunction positions EDG-7500 uniquely in the treatment landscape. This could represent a first-in-class therapy with advantages over current treatments including surgical myectomy, alcohol septal ablation, and other pharmacological approaches that often compromise systolic function.
Edgewise's positive Phase 2 data for EDG-7500 significantly strengthens their clinical pipeline and competitive positioning. The data demonstrates dose-dependent efficacy across multiple clinically relevant endpoints with a differentiated mechanism that preserves ejection fraction—a key advantage in this therapeutic area.
The rapid timeline to Phase 3 initiation (H1 2026) indicates management confidence and regulatory pathway clarity. This positions EWTX to potentially capture significant market share in the HCM treatment landscape, estimated at $1-2 billion globally.
Particularly compelling is EDG-7500's potential in both obstructive and nonobstructive HCM variants, addressing an estimated 1 in 500 people affected by this condition. The substantial improvements in patient-reported outcomes within just four weeks suggest EDG-7500 could become a preferred treatment option if confirmed in larger studies.
While safety signals including atrial fibrillation require continued vigilance, the overall profile appears manageable compared to competitor compounds. This program now represents a substantial value driver for Edgewise, with potential for accelerated development timelines if results continue to impress. The comprehensive efficacy shown across hemodynamic measurements, biomarkers, and quality-of-life metrics provides multiple paths to demonstrate value in pivotal trials.
– Phase 2 trial of EDG-7500 demonstrated rapid and clinically meaningful reductions in LVOT gradients in participants with obstructive HCM –
– Four-week treatment with EDG-7500 demonstrated substantial improvements in measures of feel and function, reductions in key cardiac biomarkers and positive trends in measures of diastolic function –
– EDG-7500 was generally well-tolerated; clinical activity was observed without meaningful changes in LVEF, including no participant with a value below
CIRRUS-HCM is a multi-part, open-label trial of EDG-7500 in individuals with HCM. In September 2024, the Company announced positive top-line data from Part A of the trial showing that a single oral dose of EDG-7500 in participants with obstructive HCM demonstrated robust reductions in left ventricular outflow tract gradient (LVOT-G) without meaningful changes in left ventricular ejection fraction (LVEF).
Part B of CIRRUS-HCM included 17 participants with obstructive HCM and Part C included 12 participants with nonobstructive HCM. Both parts of the trial evaluated the safety and efficacy of once-daily doses of 50 or 100 mg of EDG-7500 for four weeks.
In participants with obstructive HCM, EDG-7500 demonstrated meaningful dose-dependent reductions in LVOT-G at rest and post Valsalva. Participants receiving 100 mg experienced mean reductions from baseline of
In participants with nonobstructive HCM, EDG-7500 administration resulted in a dose-dependent reduction in NT-proBNP, with a
The positive results observed in participants with obstructive HCM and nonobstructive HCM were achieved without meaningful reductions in LVEF. Importantly, there were no LVEF values <
Ahmad Masri, M.D., M.S., Director of the Hypertrophic Cardiomyopathy Center at Oregon Health and Science University and CIRRUS-HCM Investigator highlighted, "These early data with EDG-7500 are encouraging, with favorable changes across multiple domains, including robust improvements in KCCQ, which suggests a potential effect of EDG-7500 on LVOT obstruction, wall stress, and diastolic dysfunction."
"After the initial single dose results and now with these data generated over four weeks of treatment, we are starting to see the profile of EDG-7500 emerge," said Anjali T. Owens, M.D., Medical Director, Center for Inherited Cardiac Disease, Associate Professor of Medicine, in the Perelman School of Medicine at the University of
"Building on the strength of clinical data to date, we are optimizing our dosing strategy in Part D of CIRRUS-HCM in participants with obstructive and nonobstructive HCM, which will inform our plans for Phase 3," said Kevin Koch, Ph.D.,
The initial data read-out from Part D is expected in the second half of 2025, with Phase 3 initiation planned for the first half of 2026.
EDG-7500 Top-line Data Webcast Event
Members of the Edgewise management team will hold a live webcast on Wednesday, April 2, 2025, at 8:30 a.m. ET to discuss the top-line data, and will be joined by leading cardiology experts, Anjali T. Owens, M.D., Medical Director, Center for Inherited Cardiac Disease, Associate Professor of Medicine, in the Perelman School of Medicine at the University of
About CIRRUS-HCM
CIRRUS-HCM, multi-center, open-label trial, in approximately 70 participants with HCM at up to 20 clinical sites in the U.S. In Part A (obstructive HCM), participants received a single dose of 50, 100 or 200 mg of EDG-7500. The primary objective of Part A was to evaluate the safety and tolerability of a single oral dose of EDG-7500 in obstructive HCM. In Part B (obstructive HCM), participants were diagnosed with obstructive HCM, LVOT peak gradient ≥30 mmHg measured at rest and ≥50 mmHg post-Valsalva as determined by echocardiography at screening, documented LVEF of ≥0.60 at screening and New York Heart Association (NYHA) classifications of Class I-III. The primary objective of Part B was to evaluate the safety and tolerability of multiple doses of EDG-7500 over four weeks in participants with obstructive HCM. In Part C (nonobstructive HCM), participants were diagnosed with nonobstructive HCM, LVOT peak gradient of < 30 mmHg measured at rest and < 50 mmHg measured during the Valsalva maneuver as determined by echocardiography as assessed at screening, maximal exercise peak LVOT gradient of < 50 mmHg as determined by echocardiography as assessed by the investigator, documented LVEF of ≥0.60 at screening and NYHA classifications of Class I-III. The primary objective of Part C was to evaluate the safety and tolerability of multiple doses of EDG-7500 over four weeks in participants with nonobstructive HCM. In Part D (obstructive and nonobstructive HCM), participants will be studied across 12 weeks of treatment, followed by a longer-term extension. The EDG-7500 dose will be optimized based on measures of NT-proBNP, KCCQ, and LVOT-G (obstructive HCM only).
To learn more about CIRRUS-HCM, visit clinicaltrials.gov, NCT06347159 (Phase 2).
About EDG-7500
EDG-7500 is a novel oral, selective, cardiac sarcomere modulator, specifically designed to slow early contraction velocity and address impaired cardiac relaxation associated with HCM and other diseases of diastolic dysfunction. The Company is enrolling the Phase 2 CIRRUS-HCM, multi-center, open-label trial, in obstructive and nonobstructive HCM in the U.S.
About Hypertrophic Cardiomyopathy
HCM is the most common form of genetic heart disease, affecting approximately one in 500 people, and is associated with reduced quality of life and an elevated risk of heart failure, abnormal heart rhythms, and sudden cardiac death. Individuals with HCM can become extremely limited in their functional capacity and ability to perform the activities of daily living. Commonly experienced symptoms include breathlessness, irregular heartbeats, chest pain, tiredness, dizziness, or even fainting. These symptoms are caused by excessive contraction and thickening (hypertrophy) of the left ventricular wall of the heart. Over time, the thickened muscle becomes stiff, making it difficult for the heart to relax and fill with blood (diastolic dysfunction). There are two major forms of HCM obstructive and nonobstructive. The obstructive HCM pathology is observed in two thirds, while nonobstructive HCM is present in one third of all individuals with HCM. Despite advancements in treatment options for some patients with HCM, there remains a significant unmet need for additional therapeutic approaches for patients.
About Edgewise Therapeutics
Edgewise Therapeutics is a leading muscle disease biopharmaceutical company developing novel therapeutics for muscular dystrophies and serious cardiac conditions. The Company's deep expertise in muscle physiology is driving a new generation of novel therapeutics. Sevasemten is an orally administered skeletal myosin inhibitor in late-stage clinical trials in Becker and Duchenne muscular dystrophies. EDG-7500 is a novel cardiac sarcomere modulator for the treatment of hypertrophic cardiomyopathy and other diseases of diastolic dysfunction, currently in Phase 2 clinical development. The entire team at Edgewise is dedicated to our mission: changing the lives of patients and families affected by serious muscle diseases. To learn more, go to: www.edgewisetx.com or follow us on LinkedIn, X, Facebook and Instagram.
Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements as that term is defined in Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Statements in this press release that are not purely historical are forward-looking statements. Such forward-looking statements include, among other things, statements regarding the potential of, and expectations regarding, EDG-7500, statements regarding the potential market opportunity for EDG-7500, statements regarding Edgewise's expectations and milestones relating to its clinical trials and clinical development of EDG-7500, including the timing of the initial data read-out from the Part D Phase 2 CIRRUS-HCM trial and the timing of the Phase 3 initiation of the CIRRUS-HCM trial, statements by Edgewise's
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